Taxodione induces apoptosis in BCR-ABL-positive cells through ROS generation

Uchihara, Yuki; Tago, Kenji; Taguchi, H; Narukawa, Yuji; Kiuchi, Fumiyuki; Tamura, Hiroomi; Funakoshi‐Tago, Megumi

doi:10.1016/j.bcp.2018.05.018

Cited by 25 publications

(17 citation statements)

References 38 publications

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“…36,37 Overproduction of ROS can induce apoptosis by promoting mitochondrial permeability and subsequently releasing proapoptotic factors in leukemia cells. 38 In this study, our results indicate that thymoquinone clearly increases the intracellular levels of ROS and the release of superoxide and cytochrome c, whereas the inhibition of ROS significantly reduces caspase-3 activation and restores the decreased cell viability in response to thymoquinone. Thus, we suggest that ROS production plays an important role in the thymoquinone-induced apoptosis of 786-O-SI3 cells.…”

Section: Discussionsupporting

confidence: 56%

“…ROS, namely, superoxide anion, hydroxyl radical, and nonradical molecules, such as hydrogen peroxide, are small molecules with short‐life span and high reactivity that are associated with the activation of various signaling cascades, such as phosphoinositide 3‐kinase/AKT, mitogen‐activated protein kinases, nuclear factor‐kappaB, and p53; these cascades can trigger autophagy and/or apoptosis and the resulting cell survival and/or cell death processes . Overproduction of ROS can induce apoptosis by promoting mitochondrial permeability and subsequently releasing proapoptotic factors in leukemia cells . In this study, our results indicate that thymoquinone clearly increases the intracellular levels of ROS and the release of superoxide and cytochrome c, whereas the inhibition of ROS significantly reduces caspase‐3 activation and restores the decreased cell viability in response to thymoquinone.…”

Section: Discussionmentioning

confidence: 90%

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Thymoquinone suppresses the proliferation of renal cell carcinoma cells via reactive oxygen species‐induced apoptosis and reduces cell stemness

Liou

Chen

Chu

et al. 2019

Environmental Toxicology

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Thymoquinone is a phytochemical compound isolated from Nigella sativa and has various biological effects, including anti‐inflammation, antioxidation, and anticancer. Here, we further investigated the anticancer effects and associated molecular mechanism of 2‐methyl‐5‐isopropyl‐1,4‐benzoquinone (thymoquinone) on human renal carcinoma cell lines 786‐O and 786‐O‐SI3 and transitional carcinoma cell line BFTC‐909. Results showed that thymoquinone significantly reduced cell viability, inhibited the colony formation of renal cancer cells, and induced cell apoptosis and mitochondrial membrane potential change in both cancer cells. In addition, thymoquinone also triggered the production of reactive oxygen species (ROS) and superoxide and the activation of apoptotic and autophagic cascade. ROS inhibition suppressed the caspase‐3 activation and restored the decreased cell viability of 786‐O‐SI3 in response to thymoquinone. Autophagy inhibition did not restore the cell viability of 786‐O‐SI3 suppressed by thymoquinone. Moreover, thymoquinone suppressed the cell sphere formation and the expression of aldehyde dehydrogenase, Nanog, Nestin, CD44, and Oct‐4 in 786‐O‐SI3 cells. The tumor‐bearing model showed that thymoquinone in vivo inhibited the growth of implanted 786‐O‐SI3 cell. All these findings indicate that thymoquinone inhibits the proliferation of 786‐O‐SI3 and BFTC‐909 cell possibly due to the induction of ROS/superoxide and the consequent apoptosis, suggesting that thymoquinone may be a potential anticancer supplement for genitourinary cancer.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 90%

Thymoquinone suppresses the proliferation of renal cell carcinoma cells via reactive oxygen species‐induced apoptosis and reduces cell stemness

Liou

Chen

Chu

et al. 2019

Environmental Toxicology

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“…3B) induce ROS accumulation in muscle cells. Therefore, high concentrations of taxodione induced apoptosis through ROS accumulation in skeletal muscle cells as previously demonstrated in cancer cells (Uchihara et al, 2018). In the RS extract, the taxodione concentration is below the cytotoxic threshold.…”

Section: Taxodione Protects Human Myoblasts and Myotubes Against H 2 supporting

confidence: 56%

“…In most cases, the pro-oxidant or antioxidant activity intimately depends on their concentrations (Bouayed & Bohn, 2010). Uchihara and collaborators (2018) have shown that taxodione induces cell toxicity at concentrations above 5 μM (Uchihara et al, 2018). This cytotoxicity has been already reported by Tayarani and collaborators in 2013.…”

Section: Taxodione Protects Human Myoblasts and Myotubes Against H 2 mentioning

confidence: 75%

The abietane diterpene taxodione contributes to the antioxidant activity of rosemary by-product in muscle tissue

Morel

Saint

Manon

et al. 2019

Journal of Functional Foods

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Research on rosemary antioxidant activity and its potential use in human health and food applications is focused on rosemary leaves and two main bioactive compounds carnosic acid and carnosol. However, many other, notyet identified molecules could be present, especially in rosemary by-products. In this study, we first showed that rosemary stem extract was the most efficient in protecting human skeletal muscle cells against oxidation. Then, using bioassay-guided fractionation, we identified taxodione, an abietane diterpene, as the main bioactive molecule in the rosemary stem extract. We demonstrated that taxodione protects skeletal muscle cells from hydrogen peroxide-induced cytotoxic damage (by monitoring ROS production, H2AX phosphorylation and CHOP gene expression). Moreover, we showed that taxodione reduces lipid and protein oxidation in postmortem mice and beef muscles during refrigerated storage. In conclusion, our results indicate that taxodione extracted from rosemary stems, a cheap and unused resource of natural antioxidants, limits oxidation in muscle tissue.

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“…Reactive oxygen species (ROS) are a group of oxygen-containing, short-lived molecules that are highly reactive [16, 17]. Previous research has indicated that overproduction ROS can induce apoptosis via opening the mitochondrial permeability transition pore and thus releasing proapoptotic factors in leukemia cells [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Usnea Acid as Multidrug Resistance (MDR) Reversing Agent against Human Chronic Myelogenous Leukemia K562/ADR Cells via an ROS Dependent Apoptosis

Wang

Niu

Qiao

et al. 2019

BioMed Research International

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Purpose. Multidrug resistance (MDR) is a major obstacle in chemotherapy of leukemia treatments. In this paper, we investigated Usnea Acid (UA) as MDR reversal agent on hematologic K562/ADR cells via ROS dependent apoptosis. Methods. CCK8 assay was used to measure cell viability rate of K562/ADR. Intracellular reactive oxygen species (ROS) generation, cell cycle distribution, cell apoptosis were measured with flow cytometry, respectively. Proteins related to apoptosis were measured by Western blot. Intracellular Adriamycin accumulation was observed by confocal microscopy and measured by flow cytometry. Results. In vitro study showed intracellular Adriamycin accumulation was remarkably increased by UA. Cell viability treated with Adr (4 μM) was decreased from 89.8% ± 4.7 to 32% ± 8.9 by combined with UA (4 μM). Adr-induced apoptosis and G1/G0 phase cell cycle arrest were remarkably increased by UA, as well as, intracellular ROS level. However, MDR reversing activity of UA was inhibited by N-acetyl cysteine (NAC), a ROS scavenger. Conclusion. These data provide compelling evidence that UA is a promising agent against MDR in leukemia cell line and suggest a promising therapeutic approach for leukemia.

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Taxodione induces apoptosis in BCR-ABL-positive cells through ROS generation

Cited by 25 publications

References 38 publications

Thymoquinone suppresses the proliferation of renal cell carcinoma cells via reactive oxygen species‐induced apoptosis and reduces cell stemness

Thymoquinone suppresses the proliferation of renal cell carcinoma cells via reactive oxygen species‐induced apoptosis and reduces cell stemness

The abietane diterpene taxodione contributes to the antioxidant activity of rosemary by-product in muscle tissue

Usnea Acid as Multidrug Resistance (MDR) Reversing Agent against Human Chronic Myelogenous Leukemia K562/ADR Cells via an ROS Dependent Apoptosis

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